High-density, long-lasting, and multi-region electrophysiological recordings using polymer electrode arrays

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to months. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track 25% of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.

[1]  Ashesh K Dhawale,et al.  Author response: Automated long-term recording and analysis of neural activity in behaving animals , 2017 .

[2]  Brian J. Kim,et al.  Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration. , 2013, Lab on a chip.

[3]  Jae-Woong Jeong,et al.  Soft Materials in Neuroengineering for Hard Problems in Neuroscience , 2015, Neuron.

[4]  Tobias Bonhoeffer,et al.  Cell-specific restoration of stimulus preference after monocular deprivation in the visual cortex , 2016, Science.

[5]  Shantanu P. Jadhav,et al.  Hippocampal-Prefrontal Reactivation during Learning Is Stronger in Awake Compared with Sleep States , 2017, The Journal of Neuroscience.

[6]  G. Buzsáki,et al.  High-Frequency Oscillations in the Output Networks of the Hippocampal–Entorhinal Axis of the Freely Behaving Rat , 1996, The Journal of Neuroscience.

[7]  Jeremy F. Magland,et al.  A Fully Automated Approach to Spike Sorting , 2017, Neuron.

[8]  A. Oeltermann,et al.  Hippocampal–cortical interaction during periods of subcortical silence , 2012, Nature.

[9]  G. Buzsáki,et al.  Preconfigured, skewed distribution of firing rates in the hippocampus and entorhinal cortex. , 2013, Cell reports.

[10]  Elad Alon,et al.  Model validation of untethered, ultrasonic neural dust motes for cortical recording , 2015, Journal of Neuroscience Methods.

[11]  G Buzsáki,et al.  Interactions between Hippocampus and Medial Septum during Sharp Waves and Theta Oscillation in the Behaving Rat , 1999, The Journal of Neuroscience.

[12]  Michale S Fee,et al.  Singing-related neural activity distinguishes four classes of putative striatal neurons in the songbird basal ganglia. , 2010, Journal of neurophysiology.

[13]  G. Buzsáki,et al.  Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus , 2017, Science.

[14]  Mati Joshua,et al.  Emergence of Context-Dependent Variability across a Basal Ganglia Network , 2014, Neuron.

[15]  J. J. Siegel,et al.  Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration , 2017, Science Advances.

[16]  G. Buzsáki Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning , 2015, Hippocampus.

[17]  N Nakabayashi,et al.  Adhesive 4-META/MMA-TBB Opaque Resin with Poly(methyl methacrylate)-coated Titanium Dioxide , 1988, Journal of dental research.

[18]  Sergey L. Gratiy,et al.  Fully integrated silicon probes for high-density recording of neural activity , 2017, Nature.

[19]  P. Layrolle,et al.  Surface treatments of titanium dental implants for rapid osseointegration. , 2007, Dental materials : official publication of the Academy of Dental Materials.

[20]  Demetris K. Roumis,et al.  Coordinated Excitation and Inhibition of Prefrontal Ensembles during Awake Hippocampal Sharp-Wave Ripple Events , 2016, Neuron.

[21]  B. McNaughton,et al.  Tetrodes markedly improve the reliability and yield of multiple single-unit isolation from multi-unit recordings in cat striate cortex , 1995, Journal of Neuroscience Methods.

[22]  Elad Alon,et al.  Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust , 2016, Neuron.

[23]  J. Csicsvari,et al.  Communication between neocortex and hippocampus during sleep in rodents , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Badrinath Roysam,et al.  Placing Sites on the Edge of Planar Silicon Microelectrodes Enhances Chronic Recording Functionality , 2018, IEEE Transactions on Biomedical Engineering.

[25]  David C. Martin,et al.  Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film , 2006, Journal of neural engineering.

[26]  G. Buzsáki,et al.  Monolithically Integrated μLEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals , 2015, Neuron.

[27]  L. Frank,et al.  New Experiences Enhance Coordinated Neural Activity in the Hippocampus , 2008, Neuron.

[28]  Vanessa M. Tolosa,et al.  Optimization of multi-layer metal neural probe design , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[29]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[30]  B. McNaughton,et al.  The Ventral Striatum in Off-Line Processing: Ensemble Reactivation during Sleep and Modulation by Hippocampal Ripples , 2004, The Journal of Neuroscience.

[31]  B. McNaughton,et al.  Hippocampus Leads Ventral Striatum in Replay of Place-Reward Information , 2009, PLoS biology.

[32]  Vanessa M. Tolosa,et al.  Insertion of flexible neural probes using rigid stiffeners attached with biodissolvable adhesive. , 2013, Journal of visualized experiments : JoVE.

[33]  Elad Eban,et al.  A cortical–hippocampal–cortical loop of information processing during memory consolidation , 2016, Nature Neuroscience.

[34]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[35]  Liesbet Lagae,et al.  In vivo characterization of the electrophysiological and astrocytic responses to a silicon neuroprobe implanted in the mouse neocortex , 2017, Scientific Reports.

[36]  M. Wilson,et al.  Coordinated memory replay in the visual cortex and hippocampus during sleep , 2007, Nature Neuroscience.

[37]  Mattias P. Karlsson,et al.  Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility , 2017, eLife.

[38]  Loren M. Frank,et al.  Towards a large-scale recording system: Demonstration of polymer-based penetrating array for chronic neural recording , 2014, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[39]  J. Muthuswamy,et al.  Brain micromotion around implants in the rodent somatosensory cortex , 2006, Journal of neural engineering.

[40]  Brad E. Pfeiffer,et al.  Autoassociative dynamics in the generation of sequences of hippocampal place cells , 2015, Science.

[41]  Mattias P. Karlsson,et al.  Author response: Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility , 2017 .

[42]  Evgueniy V. Lubenov,et al.  State-Dependent Spike-Timing Relationships between Hippocampal and Prefrontal Circuits during Sleep , 2009, Neuron.

[43]  Vanessa M. Tolosa,et al.  Polymer neural interface with dual-sided electrodes for neural stimulation and recording , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[44]  C. Lieber,et al.  Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes. , 2015, Nature materials.

[45]  A. David Redish,et al.  Complex neural codes in rat prelimbic cortex are stable across days on a spatial decision task , 2014, Front. Behav. Neurosci..

[46]  Vanessa M. Tolosa,et al.  Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo , 2008, Sensors.

[47]  Keith B. Hengen,et al.  Firing Rate Homeostasis in Visual Cortex of Freely Behaving Rodents , 2013, Neuron.

[48]  D. Leopold,et al.  Face-selective neurons maintain consistent visual responses across months , 2014, Proceedings of the National Academy of Sciences.

[49]  F. A. Wilson,et al.  Functional stability of dorsolateral prefrontal neurons. , 2004, Journal of neurophysiology.

[50]  Brad E. Pfeiffer,et al.  Hippocampal place cell sequences depict future paths to remembered goals , 2013, Nature.

[51]  T. Hromádka,et al.  Sparse Representation of Sounds in the Unanesthetized Auditory Cortex , 2008, PLoS biology.

[52]  K. Svoboda,et al.  Neural Activity in Barrel Cortex Underlying Vibrissa-Based Object Localization in Mice , 2010, Neuron.

[53]  Igor A. Lavrov,et al.  Flexible parylene-based multielectrode array technology for high-density neural stimulation and recording , 2008 .

[54]  Sean M Montgomery,et al.  Integration and Segregation of Activity in Entorhinal-Hippocampal Subregions by Neocortical Slow Oscillations , 2006, Neuron.

[55]  Stephen D. Van Hooser,et al.  Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake , 2016, Cell.

[56]  Kinam Park,et al.  Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response? , 2017, Journal of neural engineering.

[57]  Mattias P. Karlsson,et al.  A hippocampal network for spatial coding during immobility and sleep , 2016, Nature.

[58]  Ashesh K Dhawale,et al.  Automated long-term recording and analysis of neural activity in behaving animals , 2016, bioRxiv.

[59]  Teresa E. Madsen,et al.  Microfabricated polymer-based neural interface for electrical stimulation/recording, drug delivery, and chemical sensing - development , 2013, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).